Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacteria and Growth Conditions
2.2. Genome Sequencing and Analysis
2.3. Sample Preparation of Proteomic Analyses
2.4. Mass Spectrometry
2.5. Characterization and Visualization of Proteome Data
2.6. Reverse Vaccinology
2.7. Interaction of C. Pseudotuberculosis Strain 12CS0282 with Human Macrophages
2.8. Statistical Considerations
3. Results
3.1. Genome Analysis
3.1.1. Phylogenomic Characteristics of Strain 12CS0282
3.1.2. Virulence Genes in Strain 12CS0282
3.2. Proteome Analyses
3.2.1. C. Pseudotuberculosis 12CS0282 Whole Cell Proteome, Surface Fraction and Secreted Proteome Fraction
3.2.2. Metabolic Pathway Analysis
3.2.3. Identification of Virulence Proteins
3.2.4. Reverse Vaccinology
3.2.5. Interaction with Macrophages
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Reference Genome | DDH | Distance | G + C Difference |
---|---|---|---|
C. belfanti DSM 105776 T | 20.6 | 0.2129 | 1.44 |
C. diphtheriae DSM44123 T | 20.8 | 0.2116 | 1.35 |
C. pseudotuberculosis ATCC 19410 T | 99.9 | 0.0003 | 0 |
C. pseudotuberculosis DSM 20689 T | 99.9 | 0.0002 | 0 |
C. silvaticum KL0182 T | 28.5 | 0.1509 | 2.26 |
C. silvaticum W25 | 28.5 | 0.1509 | 2.25 |
C. ulcerans FRC11 | 27.6 | 0.1563 | 1.17 |
C. ulcerans NCTC 7910 T | 27.5 | 0.1568 | 1.13 |
Virulence Gene | Function | Identifier in Strain 12CS0282 |
---|---|---|
cpfrc_00029 (pld) | phospholipase D (sphingomyelin-degrading enzyme) | cp12CS0282_00124 |
cpfrc_00128 (nor) | nitric oxide reductase | cp12CS0282_00230 |
cpfrc_00386 (nanH) | neuraminidase H (sialidase) | cp12CS0282_00502 |
cpfrc_00397 | secreted subtilisin-like serine protease | cp12CS0282_00513 |
cpfrc_00491 (dtsR2) | acyl-CoA carboxylase b-subunit involved in mycolic acid synthesis | cp12CS0282_00606 |
cpfrc_00492 (dtsR1) | acetyl-CoA carboxylase b-subunit involved in fatty acid synthesis | cp12CS0282_00607 |
cpfrc_00536 | secreted SGNH-hydrolase | cp12CS0282_00649 |
cpfrc_00562 | secreted trypsin-like serine protease | cp12CS0282_00678 |
cpfrc_00565 (nrpS1) | nonribosomal peptide synthetase 1 | cp12CS0282_00682 |
cpfrc_00594 (rpfA) | resuscitation-promoting factor A (muralytic enzyme) | cp12CS0282_02168 |
cpfrc_00679 (rpfB) | resuscitation-promoting factor B (muralytic enzyme) | cp12CS0282_02083 |
cpfrc_01079 (rpfI) | resuscitation-promoting factor interacting protein (D,L-endopeptidase) | cp12CS0282_01163 |
cpfrc_01634 | secreted subtilisin-like serine protease | cp12CS0282_01728 |
cpfrc_01801 | nonribosomal peptide synthetase 2 | cp12CS0282_00926 |
cpfrc_01895 (cpp) | corynebacterial protease CP40 (serine protease) | cp12CS0282_00833 |
cpfrc_01953 (accD3) | acyl-CoA carboxylase b-subunit involved in mycolic acid synthesis | cp12CS0282_00773 |
Pathway | Theoretical Proteome | Identified Proteins | n = 3 |
---|---|---|---|
Cellular processes and signaling | 235 [11.1%] | 141 [9.8%] | 97 [9.5%] |
Environmental information processing | 67 [3.2%] | 37 [2.6%] | 25 [2.4%] |
Genetic information processing | 52 [2.5%] | 38 [2.6%] | 24 [2.3%] |
Information storage and processing | 224 [10.6%] | 142 [9.8%] | 100 [9.8%] |
Metabolism | 563 [26.6%] | 382 [26.5%] | 267 [26.1%] |
Pathogenicity | 53 [3.1%] | 45 [3.1%] | 40 [3.9%] |
Poorly characterized | 253 [11.9%] | 187 [13.0%] | 142 [13.9%] |
Uncharacterized | 671 [31.7%] | 472 [32.7%] | 328 [32.1%] |
Total | 2118 | 1444 | 1023 |
Designation | Function | Localization and Relative Abundance |
---|---|---|
cp12CS0282_00124 (pld) | phospholipase D | E (0.5%), W (0.4%) |
cp12CS0282_00230 (nor) | nitric oxide reductase | - |
cp12CS0282_00502 (nanH) | neuraminidase H | S (0.6%) |
cp12CS0282_00513 | secreted subtilisin-like serine protease | - |
cp12CS0282_00606 (dtsR2) | acyl-CoA carboxylase b-subunit involved in mycolic acid synthesis | W (0.5%) |
cp12CS0282_00607 (dtsR1) | acetyl-CoA carboxylase b-subunit involved in fatty acid synthesis | W (0.4%) |
cp12CS0282_00649 | secreted SGNH-hydrolase | S (6.3%), W (0.2%) |
cp12CS0282_00678 | secreted trypsin-like serine protease | E, S, W |
cp12CS0282_00682 (nrpS1) | nonribosomal peptide synthetase 1 | - |
cp12CS0282_02168 (rpfA) | resuscitation-promoting factor A (muralytic enzyme) | E (4.2%) |
cp12CS0282_02083 (rpfB) | resuscitation-promoting factor B (muralytic enzyme) | S (0.3%) |
cp12CS0282_01163 (rpfI) | resuscitation-promoting factor interacting protein (D,L-endopeptidase) | - |
cp12CS0282_01728 | secreted subtilisin-like serine protease | E (0.04%), S (0.3%), W (0.2%) |
cp12CS0282_0092 | nonribosomal peptide synthetase 2 | - |
cp12CS0282_00833 (cpp) | corynebacterial protease CP40 | S (0.2%) |
cp12CS0282_00773 (accD3) | acyl-CoA carboxylase b-subunit involved in mycolic acid synthesis | W (0.6%) |
Protein ID | Protein Name | MW (Da) | Stability |
---|---|---|---|
cp12CS0282_00093 | membrane protein insertase | 36,402.13 | − |
cp12CS0282_00370 | signal-transduction histidine kinase | 44,858.97 | + |
cp12CS0282_00394 | cytochrome C biogenesis protein | 60,045.54 | + |
cp12CS0282_00666 | hypothetical protein | 109,088.9 | + |
cp12CS0282_00740 | putative cell wall biosynthesis protein | 46,819.89 | − |
cp12CS0282_00766 | diacylglycerol acyltransferase/mycolyltransferase | 36,582.47 | + |
cp12CS0282_00770 | hypothetical protein | 32,832.33 | + |
cp12CS0282_00932 | hypothetical protein | 41,309.86 | + |
cp12CS0282_00991 | adaptive-response sensory-kinase | 54,403.91 | − |
cp12CS0282_01097 | NADH dehydrogenase-like protein | 49,062.65 | + |
cp12CS0282_01233 | endolytic murein transglycosylase | 41,096.36 | + |
cp12CS0282_01244 | FMN reductase | 19,296.33 | − |
cp12CS0282_01259 | protein translocase subunit | 65,933.18 | + |
cp12CS0282_01491 | penicillin-binding protein | 73,053.21 | + |
cp12CS0282_01513 | cytochrome Bc1 complex cytochrome B subunit | 110,964 | + |
cp12CS0282_01515 | cytochrome Bc1 complex cytochrome C subunit | 31,394.71 | + |
cp12CS0282_01518 | cytochrome C oxidase subunit 2 | 40,192.72 | + |
cp12CS0282_01584 | bifunctional protein | 41,939.33 | + |
cp12CS0282_01590 | hypothetical protein | 34,917.49 | − |
cp12CS0282_01839 | hypothetical protein | 34,482.87 | − |
cp12CS0282_02102 | signal transduction histidine-protein kinase/phosphatase | 56,585.5 | − |
cp12CS0282_02120 | hypothetical protein | 24,721.76 | + |
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Möller, J.; Bodenschatz, M.; Sangal, V.; Hofmann, J.; Burkovski, A. Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets. Proteomes 2022, 10, 39. https://doi.org/10.3390/proteomes10040039
Möller J, Bodenschatz M, Sangal V, Hofmann J, Burkovski A. Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets. Proteomes. 2022; 10(4):39. https://doi.org/10.3390/proteomes10040039
Chicago/Turabian StyleMöller, Jens, Mona Bodenschatz, Vartul Sangal, Jörg Hofmann, and Andreas Burkovski. 2022. "Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets" Proteomes 10, no. 4: 39. https://doi.org/10.3390/proteomes10040039
APA StyleMöller, J., Bodenschatz, M., Sangal, V., Hofmann, J., & Burkovski, A. (2022). Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets. Proteomes, 10(4), 39. https://doi.org/10.3390/proteomes10040039